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probiotics 36 Part 4 deIrdre JordAN bsc ANutr (SCIENCE OFFICER, yAKULT IRELAND) lINdA v ThomAs bsc Phd FIFsT (SCIENCE DIRECTOR, yAKULT UK LTD) There is now a reasonable body of evidence to indicate that certain probiotic strains may help support the immune system and, in general, the body’s natural defences. In this four part series on probiotics we have looked at the evidence for probiotics (i) as a risk reduction measure against antibioticassociated diarrhoea and Clostridium difficile infection; (ii) in reducing the effects of irritable bowel syndrome and associated symptoms, and more recently (iii) in the general health benefits of probiotics for the elderly. A fundamental aspect of regular probiotic consumption is their modification of the intestinal microflora such that numbers of beneficial bacteria are maintained or increased, and the effects or numbers of harmful or pathogenic bacteria are decreased. This is associated with a range of positive effects on the health and functioning of the digestive system, as well as modulation of immune function. 1 Probiotics can also have many related and more specific modes of action. By supporting the beneficial bacteria in the commensal flora, they may help inhibit the growth and reduce any harmful effects of other bacteria, antigens, toxins and carcinogens in the gut. In addition, and very importantly, probiotics can influence the immune system via the gut-associated lymphoid tissue, with positive modulation reported for the innate and even the acquired immune system (Box 1). The gut is the most vulnerable site in the body, which is why the majority of the immune system is based there in the form of the gut-associated lymphoid tissue (Figure: GALT). The small intestine contains hundreds of Peyer’s patches (concentrations of lymphoid tissues), but lymph nodes are found through the whole length of the gut (in fact, 85% of the body’s lymph nodes are estimated to be in the gut). This immune network must recognise and tolerate the commensal microflora (otherwise inflammation results), and it must also tolerate food antigens. But importantly, it must recognise and deal with pathogenic microbes. Studies with germ-free animals have clearly shown that the commensal microflora is important in educating and supporting the immune system; animals without any gut bacteria have a poorly developed immune The immune system and your gut: a closer look at an intricate relationship (Part 4 of a 4 part series) system with significantly fewer antibody-producing cells. Probiotics can support the work of the commensal flora in interacting and supporting the immune system, which explains why certain probiotics have been shown to benefit the health of the whole body, not just that of the gut. box 1: Innate and acquired immune system • The innate or non-specific immune response defends the host from infection in a non-specific manner. Cell surface receptors (Toll-like receptors) on tissue recognise and bind different microbial components. This can trigger phagocytosis and production of pro-inflammatory cytokines, which attract a local increase in white blood cells. The innate immunity is an immediate response but it does not confer long-lasting or protective immunity. Example constituents of this system are natural killer (NK) cells and phagocytic cells such as neutrophils and macrophages. Examples of Toll-like receptors are TLR-4 (recognises lipopolysaccharide, the cell wall of Gramnegative bacteria) and TLR-9 (recognises bacterial DNA). • The acquired/adaptive or specific immune response recognises and remembers specific pathogens and is thus able to mount a rapid and stronger defence when the pathogen is next encountered. Lymphocytes (T and B cells) recognise specific and different parts of a pathogen, and then can activate different pathways against it. Humoral immunity is an antibody-mediated specific response by B cell production of immunoglobulins (antibodies) such as IgA, IgG and IgE. (Humoral refers to the bodily fluids and comes from the old idea of ‘humors’ of the body). The other response is cell-mediated, mainly involving antigen-specific T cells.
Figure: Structure of GALT (Gut-associated lymphoid tissue) Figure: structure of gAlT (gut-associated lymphoid tissue) Food particles, bacteria (antigens) Epithelium T T cells B T B cells Blood system Dendritic cells B B M cell ProbIoTIcs ANd NATurAl KIller (NK) cells NK cells, part of the innate response, target tumour cells and virally-infected cells 2,3 and their activity can be influenced by the activity of the intestinal microflora. 4,5,6 One epidemiological study has shown that cancer rates are significantly higher in people with low NK cell activity, compared to those with intermediate or high NK cell activity. 7 .Low levels of NK cell activity have also been shown to be directly linked to an unhealthy lifestyle. 8,9 This may even have psychological impact: one study showed that NK cell activity declined in medical students on the day of examinations compared with one month before examinations, suggesting that mental stress can affect NK cell activity. 10 In a randomised, double-blind, placebo controlled study of 99 male smokers, probiotics were shown to restore their NK cell activity. Subjects in the treatment group and the control group were matched in terms of age, BMI, number of cigarettes smoked and health state. The intervention was a three week daily fermented milk drink containing 4x10 10 live cells of Lactobacillus casei Shirota, or a placebo drink with no bacteria. The study found that the number of cigarettes smoked every day was linked to the reduction of NK cell activity that was observed. The probiotic intervention maintained NK cell activity during the intake period compared to the placebo group in which the NK activity dropped (p=0.0002). 11 Similar results with this probiotic strain were found in another study which investigated nine healthy subjects (30-45 years), and 10 elderly subjects (55-75 years) who had relatively low levels of NK cell activity (
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